Electronic Library of Scientific Literature - © Academic Electronic Press


Volume 35 / No. 1 / 2001



David S. Goldstein, Steven M. Frank

Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD, U.S.A.;
Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD
E-mail: goldsteind@ninds.nih.gov

Objective. In the 1920s, Walter B. Cannon first described the adrenomedullary response to cold, using an ingenious in vivo bioassay based on a denervated heart preparation. Studies in humans about antecubital venous plasma concentrations of norepinephrine, the sympathetic neurotransmitter, and of epinephrine, the main adrenomedullary hormone, have suggested sympathetic nervous system activation without adrenomedullary activation. The present study used arterial levels of these catecholamines, to determine whether adrenomedullary stimulation occurs in response to decreased body temperature.
Methods. Eleven healthy volunteers underwent central intravenous infusion of warm (37°C) physiological saline, followed by infusion of the same volume of cold (4°C) saline. Brachial arterial and antecubital venous plasma concentrations of norepinephrine and epinephrine were measured by liquid chromatoraphy with electrochemical detection.
Results. Antecubital venous concentrations of norepinephrine increased markedly during cold saline infusion, with smaller and statistically borderline increases in concentrations of epinephrine. In contrast, concurrently obtained arterial concentrations of both norepinephrine and epinephrine increased significantly.
Conclusions. The results confirm Cannon’s original inference that cold evokes adrenomedullary activation. Prior studies about antecubital venous levels of catecholamines did not take into account the local hemodynamic effects of cold, which would increase extraction of circulating catecholamines and underestimate the arterial epinephrine response.
Key words: Catecholamines – Hypothermia – Adrenomedullary response – Man


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Krzysztof Kolomecki, Henryk Stepien, Magdalena Bartos, Krzysztof Kuzdak

Clinic of Endocrinological and General Surgery, Medical University of Lodz, 93-513 Poland;
Department of Experimental Endocrinology and Hormonal Diagnostics, Medical University of Lodz
E-mail: branch@poczta.onet.pl

Objective. To estimate serum levels of vascular endothelial growth factor (VEGF), metalloproteases MMP-2 (gelatinase A), MMP-3 (stromyelisine 1) and metalloprotease tissue inhibitors (TIMP-2) in patients with various benign and malignant adrenal tumours before and after surgery, as well as to evaluate if there is a correlation between serum levels of these agents and tumour types.
Methods. Serum levels of VEGF, MMP-2, -3 and TIMP-2 were estimated in 43 patients with adrenal tumour at the admission and, in case of surgery, again one month after surgery. The patients were divided into 6 groups according to the type of the tumour (I – patients with adrenal cortex carcinoma, II – with benign hormonally active adrenocortical adenomas, III – with benign, hormonally inactive adenocortical adenomas (incidentaloma), IV – with benign, hormonally active phaeochromocytomas, V - with hormonally quiescent phaeochromocytomas, VI – hormonally inactive adrenal tumours of extraglandular origin. The control group consisted of 10 healthy individuals.
Results. There was no correlation between MMP-2 serum levels and tumour types and no significant difference between MMP-2 level before and after surgery. There were no significant differences between TIMP-2 serum levels in patients with adrenal tumours and the control values. Significant increase of serum MMP-3 level was found in patients with cortex cancer and hormonally active benign adrenocortical tumours. The MMP-3 mean serum level was also significantly higher in patients with malignant incidentalomas than in those with benign ones. In all groups of patients with adrenal tumours the means serum VEGF level was significantly higher than in control patients, and it was also significantly higher in patients with malignant incidantalomas than in those with benign ones. After surgery the VEGF level decreased significantly in patients with extraglandular tumours and cortex cancers who had no recurrence.
Conclusions. Since MMP-3 and VEGF serum levels were found significantly higher in patients with malignant adrenal incidentalomas than in those with benign ones, they might be applied as markers of malignancy of incidentalomas. VEGF and MMP-3 levels decreased after tumour resection in all patients with malignant tumors and increased significantly in patients with recurrence. Therefore, they are supposed to be of prognostic value in these patients.
Key words: Adrenal tumour – Vascular endothelial growth factor – Metalloproteases – Angiogenesis

ENDOCRINE REGULATIONS, Vol. 35, 9–16, 2001

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Richard Hampl, Marta Snajderova, jan Lebl, Lidka Lisa, Marcela Dvorakova, Martin Hill, Jarmila Sulcova, Luboslav Starka

Institute of Endocrinology, 119 94 Praha, Czech Republic;
2nd Pediatric Department, 2nd Faculty of Medicine, Charles University, Praha;
Department of Pediatrics, 3rd Faculty of Medicine, Charles University, Praha
E-mail: rhampl@endo.cz

Objective. In girls with Turner’s syndrome a positive effect of growth hormone (GH) therapy on statutal growth has been well documented, in spite of the fact that the levels of GH and IGF-I in these patients are usually within the normal range. It is known that plasma levels of sex hormone-binding globulin (SHBG) are negatively associated with growth hormone (GH) and with IGF-I. Limited data on SHBG levels in these patients and only scarce reports on other than gonadal steroids in these patients are available so far. The major aim of this study was to find out whether SHBG does respond to GH treatment.
Methods. Plasma levels of SHBG, estradiol, progesterone, testosterone and the adrenal steroids and their precursors, namely cortisol, 17alpha-hydroxyprogesterone, androstenedione, dehydroepiandrosterone and its sulfate were determined in 65 patients aged 2-23 years with Turner’s syndrome. The patients were divided into 4 groups according to their actual treatment (untreated, sex steroids only, GH only, GH and sex steroids) and the differences between the groups were evaluated. With respect to dependence of SHBG and of steroids studied on age (with exception of cortisol), their values were expressed as per cents of medians of the physiological values.
Results. As expected, low levels of sex steroids were found. As to the adrenal steroids, in general, their average levels were lower than in healthy subjects but still within the physiological limits. With one exception (androstenedione), no significant differences were found between the groups. The levels of cortisol were undistinguishable from healthy subjects. Absolute as well as relative SHBG levels in untreated group and in the group treated with estrogens were normal or even lower than those reported for normal subjects of the same chronological age. Significantly reduced absolute as well as relative SHBG levels in comparison to all other groups were found in GH treated children.
Conclusion. The results indicate that SHBG may serve as a sensitive biochemical marker of the response to the GH administration.
Key words: Turner’s syndrome – Growth hormone treatment – Sex hormone binding globulin (SHBG)

ENDOCRINE REGULATIONS, Vol. 35, 17–24, 2001

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Adam Gesing, Malgorzata Karbownik, Ewa Sewerynek, Joanna Jagiela, Andrzej Lewinski

Department of Thyroidology, Institute of Endocrinology, Medical University of Lodz, 91-425 Poland
E-mail: alewin@psk2.am.lodz.pl

Objective. To examine the bromodeoxyuridine (BrdU) incorporation into DNA of thyroid follicular cells (TFC) in the remaining thyroid lobe after hemithyroidectomy (hemiTx) in 1, 2, 3 and 4 weeks time after surgery.
Methods. The experiment was performed on male Wistar rats. The Cell Proliferation Kit (Amersham, UK) was used in order to detect the incorporated BrdU. The BrdU incorporation was expressed as a BrdU labelling index (BrdULI; a number of BrdU-immunopositive TFC per 1000 TFC).
Results. 1. No statistically significant changes of BrdULI were observed between the particular groups of sham-operated (shamTx)-rats in 1, 2, 3 and 4 weeks time after surgery, and in comparison of each of them to the controls (at time ”0”); 2. In the first 2-week period after hemiTx, an increasing effect of that surgical procedure on BrdULI value was observed (the highest BrdULI value was detected 2 weeks after hemiTx); 3. In the third and fourth week after hemiTx, a decrease of BrdULI value was observed, as compared to BrdULI groups (in 1- and 2-week time after hemiTx), and to the controls (at time ”0”); 4. An increase of weight of contralateral lobe was shown in 1, 2, 3 and 4 weeks after hemiTx in comparison to thyroid lobe weight in intact rats.
Conclusions. During the first 2 weeks after hemiTx, the thyroid growth in the remaining thyroid lobe seems to ensue by hyperplasia mechanisms. The thyroid growth processes during subsequent 2 weeks (3rd and 4th) could result from other mechanisms – for example, from hypertrophy.
Key words: Bromodeoxyuridine – Labelling index – Hemithyroidectomy – Rat thyroid – Growth processes

ENDOCRINE REGULATIONS, Vol. 35, 25–30, 2001

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Y. Hirooka, J. Takagi, R. Ikai, H. Kawai, R. Nakamura, A. Nakayashiki, S. Habu, K. Otake, Y. Mori, M. Gotoh, T. Nogimori

Department of Laboratory Medicine,
Fourth Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Aichi, 480-1195, Japan,
Department of Internal Medicine, Konanshowa Hospital, Konan, Aichi, Aichi, Japan
E-mail: yhirooka@aichi-med-u.ac.jp

Objective. To develop radioimmunoassay for somatostatin receptor type 2 (SSTR2) and search for its presence in certain rat tissues.
Methods. Anti-SSTR2 antiserum has been raised in New Zealand white rabbits immunized with a conjugate of synthetic SSTR2 with bovine serum albumin. Radioiodination of SSTR2 was performed by chloramin T method followed by purification of radioiodinated material on Sephadex G-25 column.
Results. The obtained antibody did not crossreact with SSTR1, SSTR3, SSTR4, SSTR5, hypothalamic hormones, pituitary hormones, neuropeptides or gut hormones. The assay was performed with a double antibody system. SSTR2 was extracted from the tissues with acid acetone. The dilution curve of acid acetone-extracts of rat hypothalamus in the radioimmunoassay system was parallel to the standard curve. The recovery of tissue SSTR2 was about 89 % , and the intra-assay and inter-assay variations were 4.9 % and 7.8 %, respectively. SSTR2 was found in the hypothalamus, cerebrum, cerebellum, pituitary, stomach and testis.
Conclusions. These data suggest that this assay system is suitable for the estimation of SSTR2 in the tissues.
Key words: Somatostatin receptor type 2 – New radioimmunoassay – Peptide synthesis – Tissue contents in rat

ENDOCRINE REGULATIONS, Vol. 35, 31–34, 2001

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Fedor Moncek, Richard Kvetnansky, Daniela Jezova

Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava
E-mail: ueenmonc@savba.sk

Objective. Histocompatible rat strains Lewis (LEW) and Fischer 344 (F344) are often used to study hypothalamo-pituitary-adrenocortical axis function in relation to immune system activity. It has been suggested that LEW rats have a defect in the hypothalamic production of corticotropin-releasing hormone. The aim of this study was to clarify differential responsiveness of LEW and F344 rat strains to acute stress by measuring adrenocorticotropic hormone (ACTH) and corticosterone concentrations in plasma, corticosterone in adrenal cortex and proopiomelanocortin (POMC) gene expression in the pituitary and spleen.
Methods. Two separate experiments were performed. In the first, indwelling catethers were used for blood sampling from conscious animals during immobilization stress. In the second experiment, rats were immobilized for two hours and decapitated after another 3 hrs for organ collection.
Results. Our results show that LEW strain hyporeactivity was evident from significantly lower ACTH and corticosterone levels compared to those in F344 at all time intervals during stress studied. Measurement of POMC gene expression in the pituitary revealed that the difference in hormone secretion was consistent with POMC mRNA concentrations in these strains of rats. On the other hand, corticosterone concentrations in the adrenal cortex after stress were significantly higher in LEW rats compared to F344. No differences in spleen POMC mRNA concentrations between LEW and F344 rats were found.
Conclusion. The results show that differential reactivity of LEW and F344 rats is associated with different POMC gene expression in the pituitary and probably other factors on the adrenocortical level.
Key words: Lewis – Fischer – Stress – ACTH – corticosterone – POMC mRNA – pituitary – adrenals

ENDOCRINE REGULATIONS, Vol. 35, 35–41, 2001

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Christian A. Koch, Alexander O. Vortmeyer, Steve C. Huang, Salvatore Alesci, Zhengping Zhuang, Karel Pacak

National Institutes of Health, National Institute of Child Health and Human Development, PREB; National Institute of Neurological Disorders and Stroke, SNB, Bethesda, Maryland 20892, U.S.A.
E-mail: Kochc@exchange,nih.gov

We here review the literature on genetics related to pheochromocytoma. About 10 percent of these neuroendocrine tumors are hereditary and are most often associated with multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau disease, and neurofibromatosis type 1 (NF 1). Hereditary tumor syndromes such as the aforementioned ones, are ideal to study the molecular pathogenesis of tumorigenesis as opposed to sporadic tumors in which genetic alterations often merely represent epigenetic tumor progression phenomena. Recent advances in molecular genetics, especially of RET, VHL, NF1, and SDHD, helped better understand the pathogenesis of pheochromocytoma. In this paper, we not only summarize key points of genetic discoveries related to pheochromocytoma, but also report in table format all known RET germline mutations related to pheochromocytoma.
Key words:
Pheochromocytoma – Genetics – RET – VHL – NF1 – LOH

ENDOCRINE REGULATIONS, Vol. 35, 43–52, 2001

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D. Macejovα, J. Brtko

Institute of Experimental Endocrinology, Slovak Academy of Sciences, 833 06 Bratislava, Slovakia
E-mail: ueenbrtk@savba.savba.sk

The induction of mammary gland and other organ tumours by selected chemical carcinogens, 1-methyl-1-nitrosourea, 7,12-dimethylbenzanthracene, diethylnitrosoamine and azoxymethane is described and their application in experimental carcinogenesis research is discussed.
Key words: Chemically induced carcinogenesis – mammary gland – 1-methyl-1-nitrosourea, 7,12-dimethylbenzanthracene – diethylnitrosoamine – azoxymethane

ENDOCRINE REGULATIONS, Vol. 35, 53–59, 2001

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